Enrollment of Females in Randomized Trials for Glucagon-Like Peptide 1 Receptor Agonists: A Systematic Review

JACC Adv. 2024 Nov 8;3(12):101386. doi: 10.1016/j.jacadv.2024.101386. eCollection 2024 Dec.

Abstract

Background: Randomized controlled trials (RCTs) of glucagon-like peptide 1 receptor agonists (GLP-1RAs) form the basis for therapeutic recommendations for both males and females. Historically, females have been significantly underrepresented in RCTs.

Objectives: The authors sought to determine the trends of representation of females in GLP-1RA RCTs from 2007 to 2024.

Methods: We reviewed eligible studies and extracted important variables. The proportion of females among the total participants was obtained per study. This was compared over time (year) of publication and over mean age of participants. This proportion was also compared between specific types of GLP-1RA received, diabetes status, indication of therapy, and concurrent comorbidities. Participation to prevalence ratio was used to compare participation of women in clinical trials to the actual numbers of females affected by disease.

Results: We observed a declining trend in the proportion of females enrolled in RCTs compared to men (np-trend z = -2.29, P = 0.022). Studies with a higher proportion of females were those done among patients without diabetes mellitus (42% vs 39%, z = 4.53, P < 0.01), and those who were obese (42%, P < 0.01). Females were also fairly represented among smaller RCTs done in patients with heart failure (42%, P < 0.01) and chronic kidney disease (46%, P < 0.01). There was a significant underrepresentation of females in coronary heart disease (35%, P < 0.01).

Conclusions: There is a declining trend in the proportion of females enrolled in GLP-1RA RCTs compared to men. Females are fairly represented among RCTs done in heart failure and chronic kidney disease, however, significantly underrepresented for studies on coronary heart disease.

Keywords: GLP-1RA; coronary heart disease; female enrollment; heart failure; obesity; participation-to-prevalence ratio; trials.